Enhancing proline-rich antimicrobial peptide action by homodimerization: influence of bifunctional linker
Wenyi Li, Feng Lin, Andrew Hung, Anders J. Barlow, Marc‐Antoine Sani, Rita Paolini, William Singleton, James A. Holden, Mohammed Akhter Hossain, Frances Separovic, Neil M. O’Brien‐Simpson, John D. Wade
Abstract
nitric oxide production in macrophages. Molecular dynamics simulations of adsorption and permeation mechanisms of the PrAMP on a mixed lipid membrane bilayer showed that a rigid, planar tethered dimer orientation, together with the presence of fluorine atoms that provide increased bacterial membrane interaction, is critical for enhanced dimer activity. These findings highlight the advantages of use of such bifunctional tethers to produce first-in-class, potent PrAMP dimers against MDR/XDR bacterial infections.
Topics & Concepts
BifunctionalLinkerPeptideAntimicrobialProlineChemistryAction (physics)Combinatorial chemistryBiochemistryAmino acidOrganic chemistryComputer sciencePhysicsCatalysisQuantum mechanicsOperating systemAntimicrobial Peptides and ActivitiesAntibiotic Resistance in BacteriaRNA Interference and Gene Delivery